WO2010081839A1 - Cactus fruit extract - Google Patents

Abstract

The invention relates to a method for producing an aqueous formulation of a cactus fruit extract, comprising the following steps: a) providing Opuntia ficus indica fruit, b) gradually extracting the fruit by using an organic solvent in a process having 2 or more stages, wherein the solvent concentration is gradually changed, c) separating the solvent, and d) formulating the extract into an aqueous solution having an organic solvent content of less than 5 vol %, having a concentration of at least 2.5 wt %, and to the use of the formulation for the prophylaxis or therapy of veisalgia.

Description

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The invention relates to a method for producing a cactus fruit extract and its use for formulating a beverage.

The Opuntia are a plant genus of the cactus family (Cactaceae), which includes about 190 species. The use of some Opuntienarten as food has been known for several hundred years. Extracts from plant parts of the Opuntia ficus indica ("OFI") are used to treat a number of disease states, such as the plant extract is said to have a pharmacological effect for the treatment of nervous or metabolic disorders.

WO03 / 037324A1 describes an ethyl acetate extract of Opuntia ficus indica fruit, stem or dried fruit, for the prevention and treatment of Alzheimer's disease, stroke, Parkinson's disease, ischemia-induced cell and tissue damage or cardiovascular diseases such. B. also heart attack. The anti-oxidative effect of the Opuntia ficus indica extract is used to protect neural damage to nerve cells.

WO2008 / 038849A1 describes a butanol extract or acid hydrolyzate of Opuntia ficus indica which can be administered as a tablet, pill, capsule, powder, elixir, solution, syrup or aerosol and in the form of a pharmaceutical composition for the treatment of nerve diseases such as diseases of the cranial nerves, cerebrovascular diseases , cardiovascular disease, stroke, concussion, Alzheimer's, Parkinson's or myocardial infarction.

WO2005 / 041994A1 or DE10350194A1 describes the use of plant parts of opuntias and extracts prepared therefrom, for the treatment of depressive moods and illnesses or of other affective disorders which can be influenced by antidepressants, such as, for example, Eg fear and Panic disorders, bipolar depression, somatization disorders and premenstrual syndrome, as well as precursors of such diseases.

US2002 / 0102317A1 describes the recovery of biological substances from Opuntia ficus indica by extraction of the skin of the dried fruit with an organic solvent.

EP2057994A1 describes a process for producing an extract of prickly pears by extracting plant parts.

Wiese et al. (Arch Intern Med 2004: 164, 1334-1340) describes capsules that contain an extract of the peel of the fruit of Opuntia ficus indica fruit and are used because of its anti-inflammatory effect for the treatment of Veisalgia. Efficacy was demonstrated in the study by Pitter et al. (BMJ 2005: 331, 1515-1518), however, can not be confirmed.

In general, Opuntia flowers are preferably used in the literature for the production of extracts having a pharmacological action. Thus, for example, according to WO2008 / 120206A1 a water-soluble alcoholic extract of the flower of Opuntia ficus indica in capsule form is administered with a daily dose of 0.003 to 1 g per person, for the inhibition of Alphai adrenoreceptor.

Known extracts of Opuntia ficus indica are commonly used as dry preparations, such as those due to the water insoluble active ingredients and the preparation with organic solvents such as alcohol or butanol. Capsules, or highly concentrated alcoholic solutions, e.g. Elixirs, provided. However, this form of administration is often rejected by patients, especially for the treatment of mild disease states such as Veisalgia.

The symptoms of Veisalgia are expressed in malaise and impairment of a person's physical and mental performance as a result of mild alcohol intoxication. Colloquially, the terms hangover or Cat jammer in use. The triggering amount of alcohol for the symptoms can vary greatly from person to person. The symptoms described can affect the performance from hours to days. The symptoms of Veisalgia include headache, a dull feeling in the stomach, dry mouth, nausea or vomiting and general malaise. Vomiting is often accompanied by gastritis (gastric mucosal irritation), combined with loss of appetite. The mental and motor skills may be limited (eg listlessness, dizziness, difficulty concentrating, memory loss, slight shivering). Partial depressive moods up to anxiety occur.

The object of the present invention is to provide an alternative formulation of an extract of Opuntia ficus indica, which makes it possible to administer the extract as a dietary supplement or as a stimulant in a simple manner, which for mild disease states such as Veisalgia, or already Prevention of Veisalgia can be taken.

This object is achieved according to the invention by a novel process for the preparation of an aqueous formulation of a cactus fruit extract which comprises the following steps: a) providing Opuntia ficus indica fruit, b) extracting the fruit stepwise with an organic solvent in a 2- or multistage A method wherein stepwise the solvent concentration is changed, c) separating the solvent, and d) formulating the extract into an aqueous solution having an organic solvent content of less than 5% by volume, at a concentration of at least 2.5% by weight Extract.

The undesired extractant is preferably removed by conversion to a glycolic extract. As a preferred solvent used is monohydric alcohol, such as a C1-C4 alcohol, especially ethanol or butanol, ethyl acetate or acetone used. Extraction is carried out using conventional methods for plant extraction, the starting point here being the cactus fruit, preferably in peeled form, but also as whole fruit with peel or only as fruit peel. The starting material can only the fruit, preferably washed and crushed, but also include other plant material, such as flowers, stem, leaves, leaf sprouts or seeds. The fruit may be minced as a fresh fruit or dried and then treated in stepwise with the extractant. For example, the fruit is extracted with the solvent in a two-stage or multi-stage process, whereby the solvent concentration is gradually changed, for example starting with a solvent / water mixture beginning with a high concentration, for example in the range from 70% by volume to 40% by volume. or vice versa. For fractional extraction with extractants of different alcohol content, the fruit of the first fraction may serve as part of the extractant. Then each time with alcohol-water mixtures is extracted.

By gradually reducing the alcohol content, more hydrophilic ingredients are also obtained, so that the spectrum of active ingredients is much wider. In addition to the various betalaines, polyphenols and nitrogen-containing compounds such as taurine and free amino acids are additionally extracted in this way. It could be shown with this stepwise extraction, albeit with a high alcohol content, e.g. with more than 50% by volume, e.g. more than 60% by volume, in particular about 70% by volume of alcohol, beginning to produce a concentrated extract with defined active ingredients, which is nevertheless miscible, clearly or only slightly opalescent.

Various polysaccharides or hydrocolloids, for example pectin, but also lipophilic constituents, for example sterols or fat-soluble vitamins, which are rather unsuitable for aqueous drinks and may possibly delay the uptake of the desired active ingredients, do not become due to the preferred alcohol extraction co-extracted.

Preferably, a multi-step extraction in the form of a primary maceration with about 70% by volume ethanol and subsequent percolations with graded alcohol content up to about 45% by volume is carried out in order to obtain the best yields with the most interesting active substance spectrum.

In addition, by the first extraction step, maceration at an alcohol content of more than 60% by volume, e.g. at about 70% by volume, carry out a disinfection without preservative, which is not possible at lower alcohol content. This is important because this extract can also be used in non-alcoholic and non-preserved beverages. Furthermore, it was also possible to remove unwanted accompanying substances, such as mucilage.

In the next step, the extract obtained from the alcoholic stepwise extraction is optionally mixed with glycerol, and the alcohol distilled off, for example, under vacuum. The extract is then advantageously filtered.

By the method according to the invention it is possible, for example, to produce concentrated glycolic extracts from fresh Opuntia fruits without ethanol content, which dissolve clearly in aqueous media.

An exhaustive extraction process may be advantageous to maintain the ingredients in concentrated form.

Preferably, a drug or fresh-fruit extraction ratio of at least 1: 1 is set, in particular in a ratio of 2: 1 to 5: 1, preferably about 3: 1. The extract preferably contains 10 to 20%

Solids or 20-50% dry substances (non volatiles, at 100-105 ⁰ C according to Ph. Eur). After extraction, the organic solvent is separated to the extent that an aqueous solution is formed. An aqueous solution within the meaning of the invention is understood as a formulation which is substantially free of the organic solvents used for the extraction, in particular with an organic solvent content of less than 5% by volume, preferably less than 3% by volume. less than 2% by volume, less than 1% by volume, most preferably less than 0.5% by volume. An ethanol content in the extract is preferably brought below 1%, in the case of acetone or methanol, the content of the organic extractant components should not exceed 0.05% by volume. In general, this formulation is provided as a soft drink. Furthermore, the extract can also be used as an additive to alcoholic beverages and as a concentrate. Surprisingly, it has been found that the essential ingredients of the extract, such as betalaines, eg betanin, phyllocactin, indigoxanthin and polyphenols, but also organic acids, taurine, proline, glutamine and other free amino acids, find in the aqueous formulation of the invention, even at low or without alcohol content. These are not obtainable by extraction of the OFI fruit only with water.

The solvent is preferably separated off by phase separation or evaporation, in special cases also by spray drying. After concentration of the extract, this is formulated depending on the intended use and optionally preserved.

A dry extract or freeze-dried extract, but also the dried formulation according to the invention, can optionally be stored for a relatively long time before being taken up with water or with an aqueous preparation. The dry formulation is preferably also suitable as a commercial product for later bottling. According to the invention, a suitable formulation is provided which corresponds to the intended use of the beverage. Thus, a highly concentrated elixir can be provided for the prevention of Veisalgia, however, a diluted beverage to cover the increased water requirement for the treatment of already occurring clinical pictures. Likewise, orally administrable pharmaceutical formulations, such as a solution, syrup, but also dry powder, granules or effervesce for uptake with water are possible.

An extract content of at least 2.5% by weight to receive a sufficient dose with pharmacological activity is preferred. The concentration preferably used is at least 3% by weight, preferably at least 5% by weight, more preferably at least 7% by weight, 9% by weight or 10% by weight, up to 20% by weight. For special formulations, a concentration of up to 30% by weight can be selected. Particularly preferred formulations have a concentration of 3.2% by weight, for a preferred daily dose of about 5-30 g, more preferably 3-10 g. Concentrates are also offered at a concentration of about 14-16% by weight to provide a preferred daily dose of up to 50 g. Care must be taken to ensure that the formulation contains the active substances in dissolved form in order to avoid suspended matter, which leads to settling of the extract in the container. However, it may also be advantageous to provide a concentrated beverage which is mixed with an alcoholic beverage to provide an alcoholic solution of the ingredients. The formulation according to the invention can also be provided as a dilute "near water" beverage, preferably as a clear solution.

Preferably, an airtight container made of glass, PET or metal, eg aluminum is used as a container. Further ingredients of the formulation are preferably selected from the group of taurine, anthocyanins, acai berry extract, guarana, green tea extract, caffeine, fructose, sucrose, ginger ingredients, betanine, vitamins, vitamin B1 and / or B12, pantothenic acid, in particular the calcium salt, niacin, folic acid, Biotin, pyridoxine and vitamin C, minerals such as calcium or magnesium, selenium, zinc, gluconate, coenzyme Q10, L-carnitine, lipoic acid and carbonic acid, as well as other ingredients contained in an oral formulation or in a beverage or as a dietary supplement usually for consistency, flavoring or flavor enhancement, such as citric acid, ginkgo biloba extract or natural flavoring, such as prickly pear flavor. The carrier used is preferably maltodextrin.

If possible, the addition of chemical preservatives such as benzoates or sorbates is avoided.

For example, the following compositions are proposed:

Prophylaxis: "Up-front" - drink

Universell einsetzbares Produkt gemäß der „Ein-Produktstrategie"Therapy: "morning-after" drink

Universal product according to the "one-product strategy"

Ingredient Quantity / Unit

Extract Opuntia> 10g / 100ml water-soluble, slightly colored,

Guarana (natural caffeine) 50-100 mg caffeine slightly bitter

Citric acid 0.5-1.O g water-soluble, acid-soluble in water, slightly colored,

Ginkgo biloba extract or 0.1-0.5 g tasteless natural flavors water-soluble, undyed,

Taurine 0.2 g tasteless, water-soluble, undyed,

Calcium (org. Salt, gluconate) 0.2 g tasteless, water-soluble, undyed,

Magensium (org salt, gluconate) 0.18 g tasteless, water-soluble, undyed,

Pantothenic Acid (Ca-SaIz) 1.8 mg tasteless, water-soluble, undyed,

Niacin 5.4 mg tasteless, water-soluble, undyed,

Pyridoxine (HCl) 0.6 mg tasteless, water-soluble, undyed,

Vitamin C 36 mg slightly sour

The formulation is preferably provided as a durable sale product, with a shelf life of at least 6 months, preferably at least 12 months. Therefore, a method step for sterilization or preservation is proposed, which preferably comprises a physical treatment. In particular, a heat treatment or treatment with acid, for example at a pH in the range of 3.5 and 5.0, preferably pH 4, is proposed. The preferred heat treatment is a short-term heating to temperatures up to 80 ⁰ C, such as in a continuous process, a treatment at 72 ° C for a period of 1 -2 minutes, or at lower temperatures for a longer time, such as 60 ⁰ C + / - 2 ° C for a period of 30 minutes, preferably in the batch process.

In any case, careful preservative treatment is preferred in order to insignificantly reduce the ingredients, such as betalaines, polyphenols or nitrogen-containing compounds, such as taurine and free amino acids.

The formulation is provided according to the invention for the treatment of Veisalgia, in particular for the prophylaxis and therapy of Veisalgia, their symptoms and associated disease states. The preferred dose is about to prevent at least 100ml, preferably at least 200ml of the beverage, taken up to about 10 hours before drinking alcohol, but also immediately before drinking alcohol or together with the alcoholic beverage. For therapy, a dose of at least 200 ml, preferably at least 300 ml, but also at least 400 ml or more of the beverage is preferably provided within 24 hours after consumption of alcohol, for example within 12 hours. The maximum daily dose is estimated at about 2000ml to avoid malaise due to the ingredients.

The invention will be further described by the following example. Example: Preparation of an OFI extract

For the preparation of the extract whole, unpeeled, but freed from the spines, fresh Opuntia fruit were used. In the shell, the majority of pharmacologically valuable ingredients such as betalaine are present. The fruit is washed before processing, dried again and then chopped in a cutter.

The extraction method is fractionated percolation with a gradual reduction of the alcohol content. Since the opuntia fruit contains about 85% liquid, in order to get a defined extract, first a dry loss determination has to be made to calculate the amount of ethyl alcohol to be added. The extraction liquid is composed of the liquid fraction of the fruit and the added alcohol in the first fraction. A portion of the alcohol is added to avoid a fermentation process. After the necessary additional amount of the alcohol is determined and calculated, the remaining amount of alcohol is added immediately and stirred briefly. In the first batch fraction, the amount of alcohol is set at about 70% by volume (63% by weight). In the subsequent fractions, the extraction mixture is gradually reduced to 45 vol.% Alcohol, with alcohol being mixed with water beforehand.

To concentrate the extract, the collected extract fractions are concentrated in a rotary evaporator under vacuum with addition of ascorbic acid until the extract amount corresponds to a fresh plant / extract ratio of about 3: 1 and contains more than 20% dry residue. Depending on the intended use, this extract is taken up with a subset of glycerol, ethanol, glucose syrup, etc. and fed to the analysis.

Claims

A process for the preparation of an aqueous formulation of a cactus fruit extract, comprising the steps of: a) providing Opuntia ficus indica fruit, b) extracting the fruit stepwise with an organic solvent in a 2 or more step process, stepwise increasing the solvent concentration c) separating the solvent, and d) formulating the extract into an aqueous solution having an organic solvent content of less than 5% by volume, with a concentration of at least 2.5% by weight of extract. 2. The method according to claim 1, characterized in that the extract is formulated into an aqueous solution with a concentration of 2.5 to 20 wt% extract. 3. The method according to any one of claims 1 or 2, characterized in that the solvent is alcohol or ethyl acetate. 4. The method according to any one of claims 1 to 3, characterized in that the aqueous solution obtained in claim 1, item d, is further preserved by a physical treatment. 5. The method according to claim 4, characterized in that the physical treatment comprises an acid treatment and / or pasteurization. 6. Aqueous formulation containing 5 - 20 wt .-% cactus fruit extract, obtainable by a process according to any one of claims 1 to 5. 7. A formulation according to claim 6, containing at least 10 wt .-% cactus fruit extract. 8. A formulation according to any one of claims 6 or 7, characterized in that it contains further ingredients selected from the group of taurine, anthocyanins, Acaibererenextrakt, guarana, green tea extract, caffeine, fructose, sucrose, ginger ingredients, betanin, vitamins, vitamin B1 and / or B12, pantothenic acid, niacin, folic acid, biotin, pyridoxine and vitamin C, mineral substances such as calcium or magnesium, selenium, zinc, gluconate, coenzyme Q10, L-carnitine, lipoic acid and carbonic acid. 9. Use of an aqueous extract obtainable by a process according to any one of claims 1 to 5 for the manufacture of a medicament for the prophylaxis or therapy of Veisalgia. 10. Aqueous extract obtainable by a process according to any one of claims 1 to 5 for the prophylaxis or therapy of Veisalgia.